Our main objective is to extend our previous work on the template- directed synthesis of oligonucleotides in such a way as to permit the replication of any oligonucleotide containing the standard purine and pyrimidine bases. In order to obtain long oligonucleotide products rather than dimers and trimers we will work under conditions of temperature and concentration that permit an activated monomer to stack on a preformed oligomer, but which do not permit the stacking of monomers. Under these conditions, oligomers can grow, but no new dimers or trimers can form. In order to incorporate the pyrimidine nucleotides we plan to synthesize a series of special derivatives in which the nucleotide is activated by joining to an organic moiety that binds tightly to the template. In this way the incorporation of pyrimidine should be possible even though the pyrimidines themselves do not stack well enough to form an organized helix. Our secondary objective is to develop a number of solid state syntheses to the point where they can be used to produce a variety of nucleotides and nucleotide analogues. We are particularly interested in the synthesis of nucleotides that might be useful as pharmaceuticals and of alpha-, beta-, and gamma-labelled nucleoside triphosphates that could be used in nucleic acid research.